Immunogenicity Evaluation of Omicron Variant-based Vaccine and a Trivalent Vaccine in Adults Against COVID-19 in Chile (CoronaVarCL)

• ClinicalTrials.gov Identifier: NCT05593042
• Recruitment Status: Recruiting
• First Posted: October 25, 2022
• Last Update Posted: January 13, 2023
• Sponsor: Pontificia Universidad Catolica de Chile
• Collaborator: Sinovac Life Sciences Co., Ltd.
• Information provided by (Responsible Party): Pontificia Universidad Catolica de Chile

Tracking Information

• First Submitted Date: October 20, 2022
• First Posted Date: October 25, 2022
• Last Update Posted Date: January 13, 2023
• Actual Study Start Date: November 28, 2022
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 20, 2022)

• Superiority in humoral immunogenicity of the neutralizing antibodies against the Delta and Omicron variants in response to a booster dose of the trivalent vaccine compared to CoronaVac® in adults previously immunized against SARS-CoV-2. [ Time Frame: Up until 6 months after intervention ]
  Differences in the humoral immunogenicity (GMT ratio >1) of the neutralizing antibodies against the Delta and Omicron variants in response to a booster dose of the trivalent vaccine compared to CoronaVac® in adults who have initially received two doses of CoronaVac® and two booster doses with vaccines against SARS-CoV-2 different from CoronaVac® (mRNA or viral vectors (heterologous group)) will be evaluated.
• Superiority in humoral immunogenicity of neutralizing antibodies against the Omicron variant in response to a booster dose with the Omicron vaccine when compared with CoronaVac® in adults previously immunized against SARS-CoV-2. [ Time Frame: Up until 6 months after intervention ]
  Differences in the humoral immunogenicity (GMT ratio >1) of the neutralizing antibodies against the Omicron variant generated in response to a booster dose with the Omicron vaccine when compared with CoronaVac® in adults who have initially received two doses of CoronaVac® and two booster doses with vaccines against SARS-CoV-2 different from CoronaVac® (mRNA or viral vectors (heterologous group)) will be evaluated.
• Non-inferiority of neutralizing antibodies against the Omicron and Delta variants generated by a booster dose of trivalent vaccine when compared to CoronaVac® in adults previously immunized against SARS-CoV-2 in a heterologous schedule. [ Time Frame: Up until 6 months after intervention ]
  Evaluation of the non-inferiority (seroconversion rate ≥5%) of neutralizing antibodies against the Omicron and Delta variants generated by a booster dose of trivalent vaccine when compared to CoronaVac® in adults who have initially received two doses of CoronaVac® and two booster doses with vaccines from other platforms (mRNA or viral vectors (heterologous group)).
• Non-inferiority of neutralizing antibodies against the Omicron variant generated by a booster dose with Omicron vaccine when compared with CoronaVac® in adults previously immunized against SARS-CoV-2 in a heterologous schedule. [ Time Frame: Up until 6 months after intervention ]
  Evaluation of the non-inferiority (seroconversion rate ≥5%) of neutralizing antibodies against the Omicron variant generated by a booster dose with Omicron vaccine when compared with CoronaVac® in adults who have two doses of CoronaVac® and two booster doses with vaccines from other platforms (mRNA or viral vectors (heterologous group)).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 20, 2022)

• Frequency of adverse events within the 7 and 28 days after the administration of a booster dose of Omicron, trivalent or CoronaVac® vaccines. [ Time Frame: 28 days after intervention ]
  Evaluate whether there are differences in the frequency of adverse events within the 7 and 28 days after the administration of a booster dose of Omicron, trivalent or CoronaVac® vaccines.
• Serious adverse events (SAE) and adverse events of special interest (AESI) in participants who received a booster dose of the Omicron, trivalent, or CoronaVac® vaccines. [ Time Frame: Up until 6 months after intervention ]
  Follow up of serious adverse events (SAE) and adverse events of special interest (AESI) will be performed for participants who received a booster dose of the Omicron, trivalent, or CoronaVac® vaccines.
• Humoral immunogenicity against the ancestral strain induced by a booster dose with Omicron vaccine or trivalent vaccine in adults previously immunized against SARS-CoV-2 in a heterologous schedule. [ Time Frame: Up until 6 months after intervention ]
  Evaluation of the humoral immunogenicity (GMT and seroconversion rate of neutralizing antibodies) against the ancestral strain, induced by a booster dose with Omicron vaccine or trivalent vaccine in adults who have two doses of CoronaVac® and two booster doses with vaccines from other platforms (mRNA or viral vectors (heterologous group)).
• Humoral immunogenicity induced by a booster dose with Omicron or trivalent vaccine in adults previously immunized against SARS-CoV-2 in a homologous schedule. [ Time Frame: Up until 6 months after intervention ]
  To evaluate the humoral immunogenicity (GMT and seroconversion of neutralizing antibodies) induced by a booster dose with Omicron or trivalent vaccine in adults who have previously received four doses of CoronaVac® (homologous group) against the ancestral strain, the Omicron, and Delta variants.
• Cellular immunogenicity generated, in a subgroup of participants, by the administration of a booster dose with Omicron, trivalent or CoronaVac® vaccines against the ancestral strain, the Omicron and Delta variants. [ Time Frame: Up until 6 months after intervention ]
  To evaluate, in a subgroup of participants, the cellular immunogenicity (T cell activation and cytokines secretion) generated by the administration of a booster dose with Omicron, trivalent or CoronaVac® vaccines against the ancestral strain, the Omicron and Delta variants.
• Levels of neutralizing antibodies -and in a subgroup of subjects, the cellular immunity- against the ancestral, Omicron and Delta strains at 6 months after the intervention. [ Time Frame: 6 months after intervention ]
  Evaluation of the levels of neutralizing antibodies in every participant and the cellular immunity in a subgroup of subjects against the ancestral strain, the Omicron and Delta variants at 6 months after the administration of a booster dose of the Omicron, trivalent or CoronaVac® vaccines.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: October 20, 2022)

The humoral and cellular immunogenicity, in a subgroup of participants (homologous and heterologous groups), against new variants of concerns identified during the development of this trial. [ Time Frame: Up until 6 months after intervention ]

The humoral and cellular immune response elicited against new variants of concerns identified during the development of this trial will be evaluated in a subgroup of participants (homologous and heterologous groups).

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Immunogenicity Evaluation of Omicron Variant-based Vaccine and a Trivalent Vaccine in Adults Against COVID-19 in Chile
• Official Title: Phase 2, Randomized, Double-blind Study to Evaluate Immunogenicity Superiority of a Booster Dose With an Omicron or a Trivalent Vaccine Compared to CoronaVac, in Adults Immunized With Different Vaccine Schedules Against SARS-CoV-2 in Chile
• Brief Summary: Phase 2 clinical trial in adults previously vaccinated against SARS-CoV-2 in Chile with an initial schedule of two doses of CoronaVac® plus two booster doses with different vaccines. Subjects will randomly receive a third booster dose with Omicron, trivalent, or CoronaVac® vaccine. The humoral immunogenicity against COVID-19 will be compared in subjects that received the Omicron or the Trivalent vaccines with subjects that received CoronaVac® to determine the superiority of the two candidate vaccines versus CoronaVac®. Subjects will be followed for 6 months after the booster dose administration.

Detailed Description

This study will be a phase 2 randomized, double-blind, multicenter clinical trial in fully vaccinated adults, males, and females, who have previously received an initial schedule of two doses of CoronaVac® plus two booster doses with different vaccines against SARS-CoV-2 in Chile. Two groups of participants will be included: Heterologous group: subjects who had received two booster doses with mRNA or viral vector-based vaccine); and homologous group: subjects who have received two booster doses of CoronaVac® in a previous clinical trial (CoronaVac03CL).

Subjects of the heterologous group will randomly receive a booster dose with Omicron, trivalent, or CoronaVac® vaccine. On the other hand, subjects of the homologous group will randomly receive a booster dose of Omicron or trivalent vaccine.

The humoral immunogenicity against COVID-19 will be compared in subjects of the heterologous group that will receive Omicron or trivalent vaccine with subjects that will receive CoronaVac®, to determine the superiority of the two candidate vaccines versus CoronaVac®.

Subjects will be followed for 6 months after the booster dose administration.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

A specialized company designed the randomization algorithm of vaccines (IRT algorithm). The algorithm was designed considering the vaccination schedule of the subjects and the number of subjects assigned to each center. Once randomized, each participant will be assigned to a treatment branch/group. Neither the personnel administering it nor the rest of the team nor the participant will know which product was administered.

Primary Purpose: Prevention

Condition

• COVID-19
• Vaccines

Intervention

• Biological: CoronaVac®
  The active ingredient is the SARS-CoV-2 virus (CZ02 strain, ancestral) grown in Vero cells and inactivated, in aluminum hydroxide. The vaccine is preservative-free, and it is packed in pre-load syringes (0.5 mL) with 600 SU/0.5mL of inactivated SARS-CoV-2.
  Other Name: Inactivated SARS-CoV-2 Vaccine (Vero Cells) - Sinovac
• Biological: Omicron Vaccine

  An experimental intervention consisting of a booster dose of an inactivated Omicron variant vaccine.

  The active ingredient is the SARS-CoV-2 virus (Omicron variant) grown in Vero cells and inactivated, in aluminum hydroxide. The vaccine is preservative-free, packed in a pre-load syringe, and contains one dose (0.5mL) of 1200 SU of inactivated SARS-CoV-2 Omicron variant.

• Biological: Trivalent Vaccine

  An experimental intervention consisting of a booster dose of an inactivated trivalent (CZ02 strain, ancestral, Delta, and Omicron variants) variant vaccine.

  The active ingredient is the SARS-CoV-2 virus (CZ02 strain, ancestral, Delta, and Omicron variants) grown in Vero cells and inactivated, in aluminum hydroxide. The vaccine is preservative-free, and it is packed in a pre-load syringe containing one dose (0.5mL) (1200 SU of inactivated SARS-CoV-2 WT, 1200 SU of inactivated SARS-CoV-2 Delta variant, and 1200 SU of inactivated SARS-CoV-2 Omicron variant).

Study Arms

• Active Comparator: Heterologous group receiving CoronaVac®
  General population that received two doses of CoronaVac® as a primary schedule of vaccination and two booster doses as part of the national vaccination schedule with mRNA or viral vector-based vaccines; and who receive a booster dose of CoronaVac®
  Intervention: Biological: CoronaVac®
• Experimental: Heterologous group receiving Omicron vaccine
  General population that received two doses of CoronaVac® as a primary schedule of vaccination and two booster doses as part of the national vaccination schedule with mRNA or viral vector-based vaccines; and who receive a booster dose of Omicron vaccine
  Intervention: Biological: Omicron Vaccine
• Experimental: Heterologous group receiving a trivalent vaccine
  General population that received two doses of CoronaVac® as a primary schedule of vaccination and two booster doses as part of the national vaccination schedule with mRNA or viral vector-based vaccines; and who receive a booster dose of trivalent vaccine
  Intervention: Biological: Trivalent Vaccine
• Experimental: Homologous group receiving Omicron vaccine
  Participants of the CoronaVac03CL study who have received the primary regimen and two booster doses with CoronaVac® vaccine; and who receive a booster dose of Omicron vaccine
  Intervention: Biological: Omicron Vaccine
• Experimental: Homologous group receiving a trivalent vaccine
  Participants of the CoronaVac03CL study who have received the primary regimen and two booster doses with CoronaVac® vaccine and who receive a booster dose of trivalent vaccine
  Intervention: Biological: Trivalent Vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 20, 2022): 826
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2023
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adults, male or female, over 18 years of age;
• Fully vaccinated against SARS-CoV-2 with two initial doses of CoronaVac® vaccine and that have received two booster doses of a different vaccine (heterologous group) or with CoronaVac® (homologous group) at least 5 months before enrollment;
• Capable of understanding and signing the informed consent form;
• Availability and commitment to comply with study procedures and in-person and remote appointments.

Exclusion Criteria:

• Symptomatic COVID-19 diagnosed 60 days before enrollment (confirmed COVID-19 by RT-PCR or antigen test, or by being in close contact with a confirmed case);
• Pregnant women (confirmed by urine pack test) or women who plan to get pregnant within the first 3 months of the study;
• Known allergies to the vaccine components;
• Evidence of uncontrolled metabolic, neurologic#, cardiac, pulmonary, hepatic, or renal disease. Significant changes in medical treatment or hospitalizations due to worsening conditions in the last three months are indicators of uncontrolled disease or unsuccessful adherence to the treatment;
• Alteration of the immune system (neoplasms, except basal cell cancer), congenital or acquired immunodeficiencies, and uncontrolled autoimmune diseases. Significant changes in medical treatment or hospitalizations due to worsening conditions in the last three months are indicators of uncontrolled disease;
• Behavioral, psychiatric, or cognitive conditions# that, according to the study physician, impair the ability to understand and cooperate with the requirements of this trial;
• Intake of immunosuppressants within 6 months before enrollment or prescribed to be taken within the next 2 years of the study. Antineoplastic therapy, radiation, and immunosuppressants that induce tolerance to transplants, among others, are included in this category;
• Intake of corticosteroids within 3 months before enrollment or prescribed to be taken within 3 months after enrollment. The equivalent of 20 mg/day of prednisone for more than one week will be considered an immunosuppressive dose. Topical or inhaled steroids are not considered immunosuppressive drugs;
• History of anatomic or functional asplenia;
• Coagulation disorders such as coagulation factor deficiency, coagulopathy or platelet disorders, or a history of significant bleeding or bruising from intramuscular injections or venipunctures;
• Alcohol or drug abuse reported 12 months before enrollment that caused medical, professional, or family consequences;
• Have been treated with blood or immunoglobulin transfusions within 3 months before enrollment;
• Have you received any live attenuated or inactivated vaccine within 28 and 14 days prior to the enrollment or planned to receive one within the first 28 days of the study;
• Participation in another clinical trial 6 months before the enrollment or plan to participate in one 6 months after the enrollment in this trial;
• Prior participation in a SARS-CoV-2 vaccine trial different than the CoronaVac03CL trial;
• Any fever episode (body temperature ≥37.8℃) within 3 days before enrollment;

• Any other condition that according to the primary care physician, could jeopardize the safety/rights of the subject or prevent him/her from completing the protocol

  • Alzheimer's and senile dementia are exclusion criteria.

Note: Obese and smoker participants are allowed to participate.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Pablo A González, PhD; +56982287536; pagonzalez@bio.puc.cl

Contact: Alexis M Kalergis, PhD; +56981573949; akalergis@bio.puc.cl

• Listed Location Countries: Chile

Administrative Information

• NCT Number: NCT05593042
• Other Study ID Numbers: PRO-tonCOV-2001-CL
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pontificia Universidad Catolica de Chile
• Original Responsible Party: Same as current
• Current Study Sponsor: Pontificia Universidad Catolica de Chile
• Original Study Sponsor: Same as current
• Collaborators: Sinovac Life Sciences Co., Ltd.

Investigators

• Study Director: Pablo A Gonzalez, PhD; Pontificia Universidad Catolica de Chile
• Study Chair: Alexis M Kalergis, PhD; Pontificia Universidad Catolica de Chile
• Study Chair: Susan M Bueno, PhD; Pontificia Universidad Catolica de Chile
• Study Chair: Katia Abarca, MD; Pontificia Universidad Catolica de Chile

• PRS Account: Pontificia Universidad Catolica de Chile
• Verification Date: September 2022